Toxins

11 pages, 1888 KiB

Open AccessEditor’s ChoiceArticle

Discrimination of the Activity of Low-Affinity Wild-Type and High-Affinity Mutant Recombinant BoNT/B by a SIMA Cell-Based Reporter Release Assay

by Frank Neuschäfer-Rube, Andrea Pathe-Neuschäfer-Rube and Gerhard P. Püschel

Toxins 2022, 14(1), 65; https://doi.org/10.3390/toxins14010065 - 17 Jan 2022

Cited by 3 | Viewed by 3572

Abstract

Botulinum neurotoxin (BoNT) is used for the treatment of a number of ailments. The activity of the toxin that is isolated from bacterial cultures is frequently tested in the mouse lethality assay. Apart from the ethical concerns inherent to this assay, species-specific differences [...] Read more.

Botulinum neurotoxin (BoNT) is used for the treatment of a number of ailments. The activity of the toxin that is isolated from bacterial cultures is frequently tested in the mouse lethality assay. Apart from the ethical concerns inherent to this assay, species-specific differences in the affinity for different BoNT serotypes give rise to activity results that differ from the activity in humans. Thus, BoNT/B is more active in mice than in humans. The current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma–based reporter cell line (SIMA-hPOMC1-26-Gluc) was inhibited by clostridial and recombinant BoNT/A to the same extent, whereas both clostridial and recombinant BoNT/B inhibited the release to a lesser extent and only at much higher concentrations, reflecting the low activity of BoNT/B in humans. By contrast, the genetically modified BoNT/B-MY, which has increased affinity for human synaptotagmin, and the BoNT/B protein receptor inhibited luciferase release effectively and with an EC50 comparable to recombinant BoNT/A. This was due to an enhanced uptake into the reporter cells of BoNT/B-MY in comparison to the recombinant wild-type toxin. Thus, the SIMA-hPOMC1-26-Gluc cell assay is a versatile tool to determine the activity of different BoNT serotypes providing human-relevant dose-response data. Full article

(This article belongs to the Section Bacterial Toxins)

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6 pages, 241 KiB

Open AccessEditor’s ChoiceArticle

Safety of High-Dose Botulinum Toxin Injections for Parotid and Submandibular Gland Radioprotection

by Joerg Mueller, Thomas Langbein, Aditi Mishra and Richard P. Baum

Toxins 2022, 14(1), 64; https://doi.org/10.3390/toxins14010064 - 17 Jan 2022

Cited by 11 | Viewed by 4454

Abstract

Botulinum Toxin injections into salivary glands (SG) up to a total dose of 100 units IncobotulinumtoxinA (IncoA) represent the treatment of choice for sialorrhea. However, BTX might also protect SG against sialotoxic radioligand cancer therapies. The radioligand Actinium-225-PSMA effectively targets Prostate Cancer (PCa) [...] Read more.

Botulinum Toxin injections into salivary glands (SG) up to a total dose of 100 units IncobotulinumtoxinA (IncoA) represent the treatment of choice for sialorrhea. However, BTX might also protect SG against sialotoxic radioligand cancer therapies. The radioligand Actinium-225-PSMA effectively targets Prostate Cancer (PCa) metastases but inevitably destroys SG due to unintended gland uptake. A preliminary case series with regular-dose IncoA failed to reduce SG PSMA-radioligand uptake. We therefore increased IncoA dosage in combination with transdermal scopolamine until a clinically relevant SG PSMA-radioligand uptake reduction was achieved. Ten consecutive men with metastasized PCa refractory to all other cancer therapies received gradually increasing IncoA dosages as part of a compassionate use PSMA-radioligand-therapy trial. The parotid gland received six and the submandibular gland three injection points under ultrasound control, up to a maximum of 30 units IncoA per injection point. A maximum total dose of 250 units IncoA was applied with up to 170 units per parotid and 80 units per submandibular gland. Treatment was well tolerated and all side-effects were non-serious. The most frequent side-effect was dry mouth of mild severity. No dysphagia, facial weakness, chewing difficulties or systemic side-effects were observed. SG injections with IncoA up to a total dose of 250 units are safe when distributed among several injection-points under ultrasound control by an experienced physician. These preliminary findings lay the basis for future trials including BTX as major component for SG protection in established as well as newly emerging radioligand cancer therapies. Full article

(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)

3 pages, 195 KiB

Open AccessEditorial

Toxin and Immunotoxin Based Therapeutic Approaches

by Massimo Bortolotti, Letizia Polito and Andrea Bolognesi

Toxins 2022, 14(1), 63; https://doi.org/10.3390/toxins14010063 - 17 Jan 2022

Cited by 7 | Viewed by 2617

Abstract

The concept of “magic bullets”, i [...] Full article

(This article belongs to the Special Issue Toxin and Immunotoxin Based Therapeutic Approaches)

29 pages, 1849 KiB

Open AccessReview

AB₅ Enterotoxin-Mediated Pathogenesis: Perspectives Gleaned from Shiga Toxins

by Erika N. Biernbaum and Indira T. Kudva

Toxins 2022, 14(1), 62; https://doi.org/10.3390/toxins14010062 - 16 Jan 2022

Cited by 11 | Viewed by 6061

Abstract

Foodborne diseases affect an estimated 600 million people worldwide annually, with the majority of these illnesses caused by Norovirus, Vibrio, Listeria, Campylobacter, Salmonella, and Escherichia coli. To elicit infections in humans, bacterial pathogens express a combination of virulence [...] Read more.

Foodborne diseases affect an estimated 600 million people worldwide annually, with the majority of these illnesses caused by Norovirus, Vibrio, Listeria, Campylobacter, Salmonella, and Escherichia coli. To elicit infections in humans, bacterial pathogens express a combination of virulence factors and toxins. AB₅ toxins are an example of such toxins that can cause various clinical manifestations, including dehydration, diarrhea, kidney damage, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Treatment of most bacterial foodborne illnesses consists of fluid replacement and antibiotics. However, antibiotics are not recommended for infections caused by Shiga toxin-producing E. coli (STEC) because of the increased risk of HUS development, although there are conflicting views and results in this regard. Lack of effective treatment strategies for STEC infections pose a public health threat during outbreaks; therefore, the debate on antibiotic use for STEC infections could be further explored, along with investigations into antibiotic alternatives. The overall goal of this review is to provide a succinct summary on the mechanisms of action and the pathogenesis of AB₅ and related toxins, as expressed by bacterial foodborne pathogens, with a primary focus on Shiga toxins (Stx). The role of Stx in human STEC disease, detection methodologies, and available treatment options are also briefly discussed. Full article

(This article belongs to the Special Issue Shiga Toxin: Occurrence, Pathogenicity, Detection and Therapies)

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21 pages, 2252 KiB

Open AccessArticle

A Summer of Cyanobacterial Blooms in Belgian Waterbodies: Microcystin Quantification and Molecular Characterizations

by Wannes Hugo R. Van Hassel, Mirjana Andjelkovic, Benoit Durieu, Viviana Almanza Marroquin, Julien Masquelier, Bart Huybrechts and Annick Wilmotte

Toxins 2022, 14(1), 61; https://doi.org/10.3390/toxins14010061 - 16 Jan 2022

Cited by 20 | Viewed by 3785

Abstract

In the context of increasing occurrences of toxic cyanobacterial blooms worldwide, their monitoring in Belgium is currently performed by regional environmental agencies (in two of three regions) using different protocols and is restricted to some selected recreational ponds and lakes. Therefore, a global [...] Read more.

In the context of increasing occurrences of toxic cyanobacterial blooms worldwide, their monitoring in Belgium is currently performed by regional environmental agencies (in two of three regions) using different protocols and is restricted to some selected recreational ponds and lakes. Therefore, a global assessment based on the comparison of existing datasets is not possible. For this study, 79 water samples from a monitoring of five lakes in Wallonia and occasional blooms in Flanders and Brussels, including a canal, were analyzed. A Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method allowed to detect and quantify eight microcystin congeners. The mcyE gene was detected using PCR, while dominant cyanobacterial species were identified using 16S RNA amplification and direct sequencing. The cyanobacterial diversity for two water samples was characterized with amplicon sequencing. Microcystins were detected above limit of quantification (LOQ) in 68 water samples, and the World Health Organization (WHO) recommended guideline value for microcystins in recreational water (24 µg L⁻¹) was surpassed in 18 samples. The microcystin concentrations ranged from 0.11 µg L⁻¹ to 2798.81 µg L⁻¹ total microcystin. For 45 samples, the dominance of the genera Microcystis sp., Dolichospermum sp., Aphanizomenon sp., Cyanobium/Synechococcus sp., Planktothrix sp., Romeria sp., Cyanodictyon sp., and Phormidium sp. was shown. Moreover, the mcyE gene was detected in 75.71% of all the water samples. Full article

(This article belongs to the Special Issue Cyanotoxins in Bloom: Ever-Increasing Occurrence and Global Distribution of Freshwater Cyanotoxins from Planktic and Benthic Cyanobacteria)

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17 pages, 2391 KiB

Open AccessArticle

Toxicity of the Diatom Genus Pseudo-nitzschia (Bacillariophyceae): Insights from Toxicity Tests and Genetic Screening in the Northern Adriatic Sea

by Timotej Turk Dermastia, Sonia Dall’Ara, Jožica Dolenc and Patricija Mozetič

Toxins 2022, 14(1), 60; https://doi.org/10.3390/toxins14010060 - 15 Jan 2022

Cited by 15 | Viewed by 5057

Abstract

Diatoms of the genus Pseudo-nitzschia H.Peragallo are known to produce domoic acid (DA), a toxin involved in amnesic shellfish poisoning (ASP). Strains of the same species are often classified as both toxic and nontoxic, and it is largely unknown whether this difference is [...] Read more.

Diatoms of the genus Pseudo-nitzschia H.Peragallo are known to produce domoic acid (DA), a toxin involved in amnesic shellfish poisoning (ASP). Strains of the same species are often classified as both toxic and nontoxic, and it is largely unknown whether this difference is also genetic. In the Northern Adriatic Sea, there are virtually no cases of ASP, but DA occasionally occurs in shellfish samples. So far, three species—P. delicatissima (Cleve) Heiden, P. multistriata (H. Takano) H. Takano, and P. calliantha Lundholm, Moestrup, & Hasle—have been identified as producers of DA in the Adriatic Sea. By means of enzme-linked immunosorbent assay (ELISA), high-performance liquid chromatography with UV and visible spectrum detection (HPLC-UV/VIS), and liquid chromatography with tandem mass spectrometry (LC-MS/MS), we reconfirmed the presence of DA in P. multistriata and P. delicatissima and detect for the first time in the Adriatic Sea DA in P. galaxiae Lundholm, & Moestrup. Furthermore, we attempted to answer the question of the distribution of DA production among Pseudo-nitzschia species and strains by sequencing the internal transcribed spacer (ITS) phylogenetic marker and the dabA DA biosynthesis gene and coupling this with toxicity data. Results show that all subclades of the Pseudo-nitzschia genus contain toxic species and that toxicity appears to be strain dependent, often with geographic partitioning. Amplification of dabA was successful only in toxic strains of P. multistriata and the presence of the genetic architecture for DA production in non-toxic strains was thus not confirmed. Full article

(This article belongs to the Special Issue Marine Toxins from Harmful Algae and Seafood Safety)

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13 pages, 10325 KiB

Open AccessArticle

Characterization of the Composition and Biological Activity of the Venom from Vespa bicolor Fabricius, a Wasp from South China

by Yong-Hua Wu, Yu Zhang, Dan-Qiao Fang, Jing Chen, Jing-An Wang, Lin Jiang and Zhu-Fen Lv

Toxins 2022, 14(1), 59; https://doi.org/10.3390/toxins14010059 - 14 Jan 2022

Cited by 3 | Viewed by 2983

Abstract

We analyzed, for the first time, the major components and biological properties of the venom of Vespa bicolor, a wasp from South China. Using HPLC and SDS-PAGE, combined with LC–MS/MS, MALDI-TOF-MS, and NMR data to analyze V. bicolor venom (VBV), we found [...] Read more.

We analyzed, for the first time, the major components and biological properties of the venom of Vespa bicolor, a wasp from South China. Using HPLC and SDS-PAGE, combined with LC–MS/MS, MALDI-TOF-MS, and NMR data to analyze V. bicolor venom (VBV), we found that VBV contains three proteins (hyaluronidase A, phospholipase A1 (two isoforms), and antigen 5 protein) with allergenic activity, two unreported proteins (proteins 5 and 6), and two active substances with large quantities (mastoparan-like peptide 12a (Vb-MLP 12a), and 5-hydroxytryptamine (5-HT)). In addition, the antimicrobial activity of VBV was determined, and results showed that it had a significant effect against anaerobic bacteria. The minimum inhibitory concentration and minimum bactericidal concentration for Propionibacterium acnes were 12.5 µg/mL. Unsurprisingly, VBV had strong antioxidant activity because of the abundance of 5-HT. Contrary to other Vespa venom, VBV showed significant anti-inflammatory activity, even at low concentrations (1 µg/mL), and we found that Vb-MLP 12a showed pro-inflammatory activity by promoting the proliferation of RAW 264.7 cells. Cytotoxicity studies showed that VBV had similar antiproliferative effects against all tested tumor cell lines (HepG2, Hela, MCF-7, A549, and SASJ-1), with HepG2 being the most susceptible. Overall, this study on VBV has high clinical importance and promotes the development of Vespa bicolor resources. Full article

(This article belongs to the Special Issue Animal Poisons and Venoms in Drug Discovery)

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12 pages, 2661 KiB

Open AccessArticle

Antimicrobial, Insecticidal and Cytotoxic Activity of Linear Venom Peptides from the Pseudoscorpion Chelifer cancroides

by Jonas Krämer, Tim Lüddecke, Michael Marner, Elena Maiworm, Johanna Eichberg, Kornelia Hardes, Till F. Schäberle, Andreas Vilcinskas and Reinhard Predel

Toxins 2022, 14(1), 58; https://doi.org/10.3390/toxins14010058 - 14 Jan 2022

Cited by 20 | Viewed by 4429

Abstract

Linear cationic venom peptides are antimicrobial peptides (AMPs) that exert their effects by damaging cell membranes. These peptides can be highly specific, and for some, a significant therapeutic value was proposed, in particular for treatment of bacterial infections. A prolific source of novel [...] Read more.

Linear cationic venom peptides are antimicrobial peptides (AMPs) that exert their effects by damaging cell membranes. These peptides can be highly specific, and for some, a significant therapeutic value was proposed, in particular for treatment of bacterial infections. A prolific source of novel AMPs are arthropod venoms, especially those of hitherto neglected groups such as pseudoscorpions. In this study, we describe for the first time pharmacological effects of AMPs discovered in pseudoscorpion venom. We examined the antimicrobial, cytotoxic, and insecticidal activity of full-length Checacin1, a major component of the Chelifer cancroides venom, and three truncated forms of this peptide. The antimicrobial tests revealed a potent inhibitory activity of Checacin1 against several bacteria and fungi, including methicillin resistant Staphylococcus aureus (MRSA) and even Gram-negative pathogens. All peptides reduced survival rates of aphids, with Checacin1 and the C-terminally truncated Checacin1¹⁻²¹ exhibiting effects comparable to Spinosad, a commercially used pesticide. Cytotoxic effects on mammalian cells were observed mainly for the full-length Checacin1. All tested peptides might be potential candidates for developing lead structures for aphid pest treatment. However, as these peptides were not yet tested on other insects, aphid specificity has not been proven. The N- and C-terminal fragments of Checacin1 are less potent against aphids but exhibit no cytotoxicity on mammalian cells at the tested concentration of 100 µM. Full article

(This article belongs to the Special Issue Toxinologic and Pharmacological Investigation of Venomous Arthropods)

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18 pages, 2663 KiB

Open AccessReview

Snakebite Associated Thrombotic Microangiopathy and Recommendations for Clinical Practice

by Tina Noutsos, Bart J. Currie, Eranga S. Wijewickrama and Geoffrey K. Isbister

Toxins 2022, 14(1), 57; https://doi.org/10.3390/toxins14010057 - 14 Jan 2022

Cited by 25 | Viewed by 10709

Abstract

Snakebite is a significant and under-resourced global public health issue. Snake venoms cause a variety of potentially fatal clinical toxin syndromes, including venom-induced consumption coagulopathy (VICC) which is associated with major haemorrhage. A subset of patients with VICC develop a thrombotic microangiopathy (TMA). [...] Read more.

Snakebite is a significant and under-resourced global public health issue. Snake venoms cause a variety of potentially fatal clinical toxin syndromes, including venom-induced consumption coagulopathy (VICC) which is associated with major haemorrhage. A subset of patients with VICC develop a thrombotic microangiopathy (TMA). This article reviews recent evidence regarding snakebite-associated TMA and its epidemiology, diagnosis, outcomes, and effectiveness of interventions including antivenom and therapeutic plasma-exchange. Snakebite-associated TMA presents with microangiopathic haemolytic anaemia (evidenced by schistocytes on the blood film), thrombocytopenia in almost all cases, and a spectrum of acute kidney injury (AKI). A proportion of patients require dialysis, most survive and achieve dialysis free survival. There is no evidence that antivenom prevents TMA specifically, but early antivenom remains the mainstay of treatment for snake envenoming. There is no evidence for therapeutic plasma-exchange being effective. We propose diagnostic criteria for snakebite-associated TMA as anaemia with >1.0% schistocytes on blood film examination, together with absolute thrombocytopenia (<150 × 10⁹/L) or a relative decrease in platelet count of >25% from baseline. Patients are at risk of long-term chronic kidney disease and long term follow up is recommended. Full article

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18 pages, 3066 KiB

Open AccessArticle

Simplified Synthesis and Stability Assessment of Aflatoxin B₁-Lysine and Aflatoxin G₁-Lysine

by Justin B. Renaud, Jacob P. Walsh and Mark W. Sumarah

Toxins 2022, 14(1), 56; https://doi.org/10.3390/toxins14010056 - 14 Jan 2022

Cited by 9 | Viewed by 3179

Abstract

Aflatoxins B₁ (AFB₁) and G₁ (AFG₁) are carcinogenic mycotoxins that contaminate crops such as maize and groundnuts worldwide. The broadly accepted method to assess chronic human aflatoxin exposure is by quantifying the amount of aflatoxin adducted to [...] Read more.

Aflatoxins B₁ (AFB₁) and G₁ (AFG₁) are carcinogenic mycotoxins that contaminate crops such as maize and groundnuts worldwide. The broadly accepted method to assess chronic human aflatoxin exposure is by quantifying the amount of aflatoxin adducted to human serum albumin. This has been reported using ELISA, HPLC, or LC-MS/MS to measure the amount of AFB₁-lysine released after proteolysis of serum albumin. LC-MS/MS is the most accurate method but requires both isotopically labelled and unlabelled AFB₁-lysine standards, which are not commercially available. In this work, we report a simplified synthetic route to produce unlabelled, deuterated and ¹³C₆ ¹⁵N₂ labelled aflatoxin B₁-lysine and for the first-time aflatoxin G₁-lysine. Additionally, we report on the stability of these compounds during storage. This simplified synthetic approach will make the production of these important standards more feasible for laboratories performing aflatoxin exposure studies. Full article

(This article belongs to the Special Issue Mycotoxin Biomarkers: Innovation and Utility)

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12 pages, 1788 KiB

Open AccessArticle

An Integrative Analysis of Transcriptomics and Proteomics Reveals Novel Insights into the Response in the Midgut of Spodoptera frugiperda Larvae to Vip3Aa

by Minghui Jin, Yinxue Shan, Yan Peng, Ping Wang, Qi Li, Songmiao Yu, Lei Zhang and Yutao Xiao

Toxins 2022, 14(1), 55; https://doi.org/10.3390/toxins14010055 - 13 Jan 2022

Cited by 11 | Viewed by 2946

Abstract

The insecticidal Vip3 proteins, secreted by Bacillus thuringiensis (Bt) during its vegetative growth phase, are currently used in Bt crops to control insect pests, and are genetically distinct from known insecticidal Cry proteins. Compared with Cry toxins, the mechanisms of Vip3 [...] Read more.

The insecticidal Vip3 proteins, secreted by Bacillus thuringiensis (Bt) during its vegetative growth phase, are currently used in Bt crops to control insect pests, and are genetically distinct from known insecticidal Cry proteins. Compared with Cry toxins, the mechanisms of Vip3 toxins are still poorly understood. Here, the responses of Spodoptera frugiperda larvae after Vip3Aa challenge are characterized. Using an integrative analysis of transcriptomics and proteomics, we found that Vip3Aa has enormous implications for various pathways. The downregulated genes and proteins were mainly enriched in metabolic pathways, including the insect hormone synthesis pathway, whereas the upregulated genes and proteins were mainly involved in the caspase-mediated apoptosis pathway, along with the MAPK signaling and endocytosis pathways. Moreover, we also identified some important candidate genes involved in apoptosis and MAPKs. The present study shows that exposure of S. frugiperda larvae to Vip3Aa activates apoptosis pathways, leading to cell death. The results will promote our understanding of the host response process to the Vip3Aa, and help us to better understand the mode of action of Vip3A toxins. Full article

(This article belongs to the Special Issue Insect Resistance to Bacillus thuringiensis Toxins)

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7 pages, 810 KiB

Open AccessEditor’s ChoiceReview

Establishing Cell Models to Understand Cellular Toxicity: Lessons Learned from an Unconventional Cell Type

by Tino Vollmer and Bernd Stegmayr

Toxins 2022, 14(1), 54; https://doi.org/10.3390/toxins14010054 - 12 Jan 2022

Viewed by 2951

Abstract

The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with [...] Read more.

The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with the expected reactions in human patients and studies on one organ system are limited in capturing the complexity of the uremic situation. In this narrative review, we present aspects relevant for cellular toxicity research based on our previous establishment of a human spermatozoa-based cell model, as follows: (i) applicability to compare the effects of more than 100 uremic substances, (ii) detection of the protective effects of uremic substances by the cellular responses towards the uremic milieu, (iii) inclusion of the drug milieu for cellular function, and (iv) transferability for clinical application, e.g., hemodialysis. Our technique allows the estimation of cell viability, vitality, and physiological state, not only restricted to acute or chronic kidney toxicity but also for other conditions, such as intoxications of unknown substances. The cellular models can clarify molecular mechanisms of action of toxins related to human physiology and therapy. Identification of uremic toxins retained during acute and chronic kidney injury enables further research on the removal or degradation of such products. Full article

(This article belongs to the Special Issue Uremic Toxins and Urinary Acute Kidney Injury Biomarkers)

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22 pages, 782 KiB

Open AccessReview

BoNT/A in the Urinary Bladder—More to the Story than Silencing of Cholinergic Nerves

by Hodan Ibrahim, Jacquie Maignel, Fraser Hornby, Donna Daly and Matthew Beard

Toxins 2022, 14(1), 53; https://doi.org/10.3390/toxins14010053 - 12 Jan 2022

Cited by 6 | Viewed by 3203

Abstract

Botulinum neurotoxin (BoNT/A) is an FDA and NICE approved second-line treatment for overactive bladder (OAB) in patients either not responsive or intolerant to anti-cholinergic drugs. BoNT/A acts to weaken muscle contraction by blocking release of the neurotransmitter acetyl choline (ACh) at neuromuscular junctions. [...] Read more.

Botulinum neurotoxin (BoNT/A) is an FDA and NICE approved second-line treatment for overactive bladder (OAB) in patients either not responsive or intolerant to anti-cholinergic drugs. BoNT/A acts to weaken muscle contraction by blocking release of the neurotransmitter acetyl choline (ACh) at neuromuscular junctions. However, this biological activity does not easily explain all the observed effects in clinical and non-clinical studies. There are also conflicting reports of expression of the BoNT/A protein receptor, SV2, and intracellular target protein, SNAP-25, in the urothelium and bladder. This review presents the current evidence of BoNT/A’s effect on bladder sensation, potential mechanisms by which it might exert these effects and discusses recent advances in understanding the action of BoNT in bladder tissue. Full article

(This article belongs to the Special Issue Structure and Function of Clostridial and Botulinum-Like Neurotoxins)

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10 pages, 912 KiB

Open AccessArticle

Knockout of ABC Transporter ABCG4 Gene Confers Resistance to Cry1 Proteins in Ostrinia furnacalis

by Qing Gao, Yaling Lin, Xiuping Wang, Dapeng Jing, Zhenying Wang, Kanglai He, Shuxiong Bai, Yongjun Zhang and Tiantao Zhang

Toxins 2022, 14(1), 52; https://doi.org/10.3390/toxins14010052 - 12 Jan 2022

Cited by 7 | Viewed by 2567

Abstract

Ostrinia furnacalis is an important borer on maize. Long-term and large-scale planting of transgenic corn has led O. furnacalis evolving resistance and reducing the control effect. Recently, high levels of resistance to Bt Cry1 toxins have been reported to be genetically linked to [...] Read more.

Ostrinia furnacalis is an important borer on maize. Long-term and large-scale planting of transgenic corn has led O. furnacalis evolving resistance and reducing the control effect. Recently, high levels of resistance to Bt Cry1 toxins have been reported to be genetically linked to the mutation or down-regulation of ABC transporter subfamily G gene ABCG4 in O. furnacalis. In order to further determine the relationship between ABCG4 gene and the resistance to Cry1 toxins in O. furnacalis, the novel CRISPR/Cas9 genome engineering system was utilized to successfully construct ABCG4-KO knockout homozygous strain. Bioassay results indicated that an ABCG4-KO strain had a higher resistance to Cry1 proteins compared with a susceptible strain (ACB-BtS). The result indicates that the ABCG4 gene may act as a receptor of the Bt Cry1 toxin in O. furnacalis. Furthermore, the development time was significantly changed in the early stage ABCG4-KO larvae, and the population parameters were also significantly changed. In summary, our CRISPR/Cas9-mediated genome editing study presents evidence that ABCG4 gene is a functional receptor for Bt Cry1 toxins, laying the foundation for further clarification of the Bt resistance mechanism. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Bacterial Toxins)

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14 pages, 30308 KiB

Open AccessArticle

Temporal Prediction of Paralytic Shellfish Toxins in the Mussel Mytilus galloprovincialis Using a LSTM Neural Network Model from Environmental Data

by Jisun Shin and Soo Mee Kim

Toxins 2022, 14(1), 51; https://doi.org/10.3390/toxins14010051 - 12 Jan 2022

Cited by 1 | Viewed by 1813

Abstract

Paralytic shellfish toxins (PSTs) are produced mainly by Alexandrium catenella (formerly A. tamarense). Since 2000, the National Institute of Fisheries Science (NIFS) has been providing information on PST outbreaks in Korean coastal waters at one- or two-week intervals. However, a daily forecast [...] Read more.

Paralytic shellfish toxins (PSTs) are produced mainly by Alexandrium catenella (formerly A. tamarense). Since 2000, the National Institute of Fisheries Science (NIFS) has been providing information on PST outbreaks in Korean coastal waters at one- or two-week intervals. However, a daily forecast is essential for immediate responses to PST outbreaks. This study aimed to predict the outbreak timing of PSTs in the mussel Mytilus galloprovincialis in Jinhae Bay and along the Geoje coast in the southern coast of the Korea Peninsula. We used a long-short-term memory (LSTM) neural network model for temporal prediction of PST outbreaks from environmental data, such as water temperature (WT), tidal height, and salinity, measured at the Geojedo, Gadeokdo, and Masan tidal stations from 2006 to 2020. We found that PST outbreaks is gradually accelerated during the three years from 2018 to 2020. Because the in-situ environmental measurements had many missing data throughout the time span, we applied LSTM for gap-filling of the environmental measurements. We trained and tested the LSTM models with different combinations of environmental factors and the ground truth timing data of PST outbreaks for 5479 days as input and output. The LSTM model trained from only WT had the highest accuracy (0.9) and lowest false-alarm rate. The LSTM-based temporal prediction model may be useful as a monitoring system of PSP outbreaks in the coastal waters of southern Korean. Full article

(This article belongs to the Section Marine and Freshwater Toxins)

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22 pages, 1472 KiB

Open AccessReview

Aggregatibacter actinomycetemcomitans as the Aetiological Cause of Rheumatoid Arthritis: What Are the Unsolved Puzzles?

by Sung Cheng Looh, Zoey May Pheng Soo, Jia Jia Wong, Hok Chai Yam, Sook Khuan Chow and Jung Shan Hwang

Toxins 2022, 14(1), 50; https://doi.org/10.3390/toxins14010050 - 11 Jan 2022

Cited by 13 | Viewed by 4040

Abstract

Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as Aggregatibacter actinomycetemcomitans (Aa). LtxA is associated with elevated levels of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. LtxA targets leukocytes and triggers an influx of [...] Read more.

Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as Aggregatibacter actinomycetemcomitans (Aa). LtxA is associated with elevated levels of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. LtxA targets leukocytes and triggers an influx of extracellular calcium into cytosol. The current proposed model of LtxA-mediated hypercitrullination involves the dysregulated activation of peptidylarginine deiminase (PAD) enzymes to citrullinate proteins, the release of hypercitrullinated proteins through cell death, and the production of autoantigens recognized by ACPA. Although model-based evidence is yet to be established, its interaction with the host’s immune system sparked interest in the role of LtxA in RA. The first part of this review summarizes the current knowledge of Aa and LtxA. The next part highlights the findings of previous studies on the association of Aa or LtxA with RA aetiology. Finally, we discuss the unresolved aspects of the proposed link between LtxA of Aa and RA. Full article

(This article belongs to the Special Issue Bacterial Exotoxins and Their Impact on Host–Pathogen Interaction in Animals and Humans)

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12 pages, 3916 KiB

Open AccessArticle

Optimization of Surface-Enhanced Raman Spectroscopy Detection Conditions for Interaction between Gonyautoxin and Its Aptamer

by Yan Liu, Lijuan He, Yunli Zhao, Yongbing Cao, Zhiguo Yu and Feng Lu

Toxins 2022, 14(1), 49; https://doi.org/10.3390/toxins14010049 - 11 Jan 2022

Cited by 1 | Viewed by 2201

Abstract

This study aimed to optimize the detection conditions for surface-enhanced Raman spectroscopy (SERS) of single-stranded DNA (ssDNA) in four different buffers and explore the interaction between gonyautoxin (GTX1/4) and its aptamer, GO18. The influence of the silver colloid solution and MgSO₄ concentration [...] Read more.

This study aimed to optimize the detection conditions for surface-enhanced Raman spectroscopy (SERS) of single-stranded DNA (ssDNA) in four different buffers and explore the interaction between gonyautoxin (GTX1/4) and its aptamer, GO18. The influence of the silver colloid solution and MgSO₄ concentration (0.01 M) added under four different buffered conditions on DNA SERS detection was studied to determine the optimum detection conditions. We explored the interaction between GTX1/4 and GO18 under the same conditions as those in the systematic evolution of ligands by exponential enrichment technique, using Tris-HCl as the buffer. The characteristic peaks of GO18 and its G-quadruplex were detected in four different buffer solutions. The change in peak intensity at 1656 cm⁻¹ confirmed that the binding site between GTX1/4 and GO18 was in the G-quadruplex plane. The relative intensity of the peak at 1656 cm⁻¹ was selected for the GTX1/4–GO18 complex (I₁₆₅₆/I₁₀₉₉) to plot the ratio of GTX1/4 in the Tris-HCl buffer condition (including 30 μL of silver colloid solution and 2 μL of MgSO₄), and a linear relationship was obtained as follows: Y = 0.1867X + 1.2205 (R² = 0.9239). This study provides a basis for subsequent application of SERS in the detection of ssDNA, as well as the binding of small toxins and aptamers. Full article

(This article belongs to the Special Issue Marine Biotoxins: Predicting and Cumulative Risk Assessment)

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16 pages, 2863 KiB

Open AccessArticle

Neurotoxic Potential of Deoxynivalenol in Murine Brain Cell Lines and Primary Hippocampal Cultures

by Christiane Kruse Fæste, Anita Solhaug, Marion Gaborit, Florian Pierre and Dominique Massotte

Toxins 2022, 14(1), 48; https://doi.org/10.3390/toxins14010048 - 10 Jan 2022

Cited by 9 | Viewed by 2629

Abstract

Chronic exposure to the mycotoxin deoxynivalenol (DON) from grain-based food and feed affects human and animal health. Known consequences include entereopathogenic and immunotoxic defects; however, the neurotoxic potential of DON has only come into focus more recently due to the observation of behavioural [...] Read more.

Chronic exposure to the mycotoxin deoxynivalenol (DON) from grain-based food and feed affects human and animal health. Known consequences include entereopathogenic and immunotoxic defects; however, the neurotoxic potential of DON has only come into focus more recently due to the observation of behavioural disorders in exposed farm animals. DON can cross the blood-brain barrier and interfere with the homeostasis/functioning of the nervous system, but the underlying mechanisms of action remain elusive. Here, we have investigated the impact of DON on mouse astrocyte and microglia cell lines, as well as on primary hippocampal cultures by analysing different toxicological endpoints. We found that DON has an impact on the viability of both glial cell types, as shown by a significant decrease of metabolic activity, and a notable cytotoxic effect, which was stronger in the microglia. In astrocytes, DON caused a G1 phase arrest in the cell cycle and a decrease of cyclic-adenosine monophosphate (cAMP) levels. The pro-inflammatory cytokine tumour necrosis factor (TNF)-α was secreted in the microglia in response to DON exposure. Furthermore, the intermediate filaments of the astrocytic cytoskeleton were disturbed in primary hippocampal cultures, and the dendrite lengths of neurons were shortened. The combined results indicated DON’s considerable potential to interfere with the brain cell physiology, which helps explain the observed in vivo neurotoxicological effects. Full article

(This article belongs to the Section Mycotoxins)

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11 pages, 264 KiB

Open AccessArticle

Video-Urodynamic Characteristics and Predictors of Switching from Botulinum Neurotoxin a Injection to Augmentation Enterocystoplasty in Spinal Cord Injury Patients

by Chih-Chieh Lin and Hann-Chorng Kuo

Toxins 2022, 14(1), 47; https://doi.org/10.3390/toxins14010047 - 10 Jan 2022

Cited by 5 | Viewed by 1822

Abstract

Botulinum neurotoxin type A (BoNT-A) injection and augmentation enterocystoplasty (AE) are alternative and effective management strategies for neurogenic detrusor overactivity (NDO) refractory to pharmacotherapy. A great majority of patients with spinal cord injury (SCI) may, however, prefer BoNT-A injections to AE, due to [...] Read more.

Botulinum neurotoxin type A (BoNT-A) injection and augmentation enterocystoplasty (AE) are alternative and effective management strategies for neurogenic detrusor overactivity (NDO) refractory to pharmacotherapy. A great majority of patients with spinal cord injury (SCI) may, however, prefer BoNT-A injections to AE, due to the less invasive characteristics. In this study we evaluated the influence of various video-urodynamic study (VUDS) parameters in SCI patients who continuously received repeat BoNT-A detrusor injections or switched to AE to improve their bladder conditions. We compared the changes in the urodynamic parameters before and after each mode of treatment. In this retrospective study, all SCI patients with refractory NDO who had received at least one BoNT-A injection were enrolled. VUDS was performed before and after both BoNT-A injection and AE. All of the urodynamic parameters of the storage and micturition—including the bladder capacity of every sensation, maximal flow rate (Qmax), post-voiding residual volume, detrusor pressure at Qmax, and bladder contractility index—were recorded. A total of 126 patients, including 46 women and 80 men, with a mean age of 41.8 ± 13.1 years, were recruited for this study. All of the patients receiving either BoNT-A injection or AE had a statistically significant increase of bladder capacity at every time-point during filling and a decrease in detrusor pressure at Qmax during voiding. Patients who switched from BoNT-A to AE had greater improvements in their urodynamic parameters when compared with those who continued with BoNT-A injections. Accordingly, SCI patients receiving BoNT-A injections but experiencing few improvements in their urodynamic parameters should consider switching to AE to achieve a better storage function and bladder capacity. Full article

(This article belongs to the Special Issue Botulinum Toxins: Old and New Applications in Humans and Animals for the Treatment of Lower Urinary Tract Conditions)

17 pages, 1103 KiB

Open AccessArticle

Ciguatoxin Detection in Flesh and Liver of Relevant Fish Species from the Canary Islands

by María José Ramos-Sosa, Natalia García-Álvarez, Andres Sanchez-Henao, Freddy Silva Sergent, Daniel Padilla, Pablo Estévez, María José Caballero, José Luís Martín-Barrasa, Ana Gago-Martínez, Jorge Diogène and Fernando Real

Toxins 2022, 14(1), 46; https://doi.org/10.3390/toxins14010046 - 9 Jan 2022

Cited by 17 | Viewed by 4194

Abstract

The Canary Islands are a ciguatoxin (CTX) hotspot with an established official monitoring for the detection of CTX in fish flesh from the authorised points of first sale. Fish caught by recreational fishermen are not officially tested and the consumption of toxic viscera [...] Read more.

The Canary Islands are a ciguatoxin (CTX) hotspot with an established official monitoring for the detection of CTX in fish flesh from the authorised points of first sale. Fish caught by recreational fishermen are not officially tested and the consumption of toxic viscera or flesh could lead to ciguatera poisoning (CP). The objectives of this study were to determine the presence of CTX-like toxicity in relevant species from this archipelago, compare CTX levels in liver and flesh and examine possible factors involved in their toxicity. Sixty amberjack (Seriola spp.), 27 dusky grouper (Epinephelus marginatus), 11 black moray eels (Muraena helena) and 11 common two-banded seabream (Diplodus vulgaris) were analysed by cell-based assay (CBA) and Caribbean ciguatoxin-1 (C-CTX1) was detected by liquid chromatography mass spectrometry (LC-MS/MS) in all these species. Most of the liver displayed higher CTX levels than flesh and even individuals without detectable CTX in flesh exhibited hepatic toxicity. Black moray eels stand out for the large difference between CTX concentration in both tissues. None of the specimens with non-toxic liver showed toxicity in flesh. This is the first evidence of the presence of C-CTX1 in the common two-banded seabream and the first report of toxicity comparison between liver and muscle from relevant fish species captured in the Canary Islands. Full article

(This article belongs to the Special Issue Ciguatoxins 2022–2023)

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16 pages, 3865 KiB

Open AccessEditor’s ChoiceArticle

Taqman qPCR Quantification and Fusarium Community Analysis to Evaluate Toxigenic Fungi in Cereals

by Elina Sohlberg, Vertti Virkajärvi, Päivi Parikka, Sari Rämö, Arja Laitila and Tuija Sarlin

Toxins 2022, 14(1), 45; https://doi.org/10.3390/toxins14010045 - 6 Jan 2022

Cited by 10 | Viewed by 3498

Abstract

Fusarium head blight (FHB) is an economically important plant disease. Some Fusarium species produce mycotoxins that cause food safety concerns for both humans and animals. One especially important mycotoxin-producing fungus causing FHB is Fusarium graminearum. However, Fusarium species form a disease complex [...] Read more.

Fusarium head blight (FHB) is an economically important plant disease. Some Fusarium species produce mycotoxins that cause food safety concerns for both humans and animals. One especially important mycotoxin-producing fungus causing FHB is Fusarium graminearum. However, Fusarium species form a disease complex where different Fusarium species co-occur in the infected cereals. Effective management strategies for FHB are needed. Development of the management tools requires information about the diversity and abundance of the whole Fusarium community. Molecular quantification assays for detecting individual Fusarium species and subgroups exist, but a method for the detection and quantification of the whole Fusarium group is still lacking. In this study, a new TaqMan-based qPCR method (FusE) targeting the Fusarium-specific elongation factor region (EF1α) was developed for the detection and quantification of Fusarium spp. The FusE method was proven as a sensitive method with a detection limit of 1 pg of Fusarium DNA. Fusarium abundance results from oat samples correlated significantly with deoxynivalenol (DON) toxin content. In addition, the whole Fusarium community in Finnish oat samples was characterized with a new metabarcoding method. A shift from F. culmorum to F. graminearum in FHB-infected oats has been detected in Europe, and the results of this study confirm that. These new molecular methods can be applied in the assessment of the Fusarium community and mycotoxin risk in cereals. Knowledge gained from the Fusarium community analyses can be applied in developing and selecting effective management strategies for FHB. Full article

(This article belongs to the Special Issue Selected Papers from the 15th European Fusarium Seminar)

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14 pages, 1060 KiB

Open AccessArticle

Significant Long-Lasting Improvement after Switch to Incobotulinum Toxin in Cervical Dystonia Patients with Secondary Treatment Failure

by Harald Hefter, Beyza Ürer, Raphaela Brauns, Dietmar Rosenthal, Sven G. Meuth, John-Ih Lee, Philipp Albrecht and Sara Samadzadeh

Toxins 2022, 14(1), 44; https://doi.org/10.3390/toxins14010044 - 6 Jan 2022

Cited by 8 | Viewed by 2568

Abstract

Under continuous long-term treatment with abo- or onabotulinum toxin type A (BoNT/A), ~10 to 15% of patients with cervical dystonia (CD) will develop neutralizing antibodies and reduced responsiveness over an ~10-year treatment period. Among the botulinum neurotoxin type A preparations so far licensed [...] Read more.

Under continuous long-term treatment with abo- or onabotulinum toxin type A (BoNT/A), ~10 to 15% of patients with cervical dystonia (CD) will develop neutralizing antibodies and reduced responsiveness over an ~10-year treatment period. Among the botulinum neurotoxin type A preparations so far licensed for CD, incobotulinum toxin A (incoBoNT/A; Xeomin^®) is the only one without complex proteins. Whether CD patients with treatment failure under abo- or onaBoNT/A may still respond to incoBoNT/A is unknown. In this cross-sectional, retrospective study, 64 CD patients with secondary treatment failure after abo- or onaBoNT/A therapy who were switched to incoBoNT/A were compared to 34 CD patients exclusively treated with incoBoNT/A. The initial clinical severity of CD, best outcome during abo- or onaBoNT/A therapy, severity at the time of switching to incoBoNT/A and severity at recruitment, as well as all corresponding doses, were analyzed. Furthermore, the impact of neutralizing antibodies (NABs) on the long-term outcome of incoBoNT/A therapy was evaluated. Patients significantly improved after the switch to incoBoNT/A (p < 0.001) but did not reach the improvement level obtained before the development of partial secondary treatment failure or that of patients who were exclusively treated with incoBoNT/A. No difference between abo- and onaBoNT/A pretreatments or between the long-term outcomes of NAB-positive and NAB-negative patients was found. The present study demonstrates significant long-term improvement after a switch to incoBoNT/A in patients with preceding secondary treatment failure after abo- or onaBoNT/A therapy and confirms the low antigenicity of incoBoNT/A. Full article

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15 pages, 1710 KiB

Open AccessArticle

Measuring Effects on Pain and Quality of Life after Abobotulinum Toxin A Injections in Children with Cerebral Palsy

by Christian Wong, Ian Westphall and Josephine Sandahl Michelsen

Toxins 2022, 14(1), 43; https://doi.org/10.3390/toxins14010043 - 5 Jan 2022

Cited by 6 | Viewed by 2858

Abstract

Sixty-seven percent of children with cerebral palsy (CCP) experience pain. Pain is closely interrelated to diminished quality of life. Despite this, pain is an overlooked and undertreated clinical problem. The objective of this study was to examine the analgesic effect of a single [...] Read more.

Sixty-seven percent of children with cerebral palsy (CCP) experience pain. Pain is closely interrelated to diminished quality of life. Despite this, pain is an overlooked and undertreated clinical problem. The objective of this study was to examine the analgesic effect of a single lower extremity intramuscular injection of Abobotulinum toxin A/Dysport in CCP. Twenty-five CCP with at least moderate pain (r-FLACC ≥ 4) during passive range of motion were included. Localized pain and pain in everyday living were measured by r-FLACC and the Paediatric Pain Profile (PPP), respectively. Functional improvements were evaluated by the goal attainment scale (SMART GAS). Quality of life was evaluated by either the CPCHILD or the CP-QOL. The subjects were evaluated at baseline before injection, then after 4, 12, and 28 weeks. Twenty-two subjects had a significant mean and maximum localized pain reduction (p < 0.001) at four weeks post-treatment in 96% (21/22). The reduction was maintained at 12 (19/19) and 28 weeks (12/15). Daily pain evaluated by the PPP was significantly reduced and functional SMART GAS goals were significantly achieved from 4 to 28 weeks. Quality of life improved significantly at four weeks (CPCHILD). Significant functional gains and localized and daily pain reduction were seen from 4 to 28 weeks. Full article

(This article belongs to the Special Issue Treatment Applications of Botulinum Toxins in the Multidisciplinary and Integrated Management of Pain Syndromes)

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13 pages, 834 KiB

Open AccessArticle

High-Throughput Determination of Major Mycotoxins with Human Health Concerns in Urine by LC-Q TOF MS and Its Application to an Exposure Study

by Noelia Pallarés, Dionisia Carballo, Emilia Ferrer, Yelko Rodríguez-Carrasco and Houda Berrada

Toxins 2022, 14(1), 42; https://doi.org/10.3390/toxins14010042 - 5 Jan 2022

Cited by 8 | Viewed by 2773

Abstract

Human biomonitoring constitutes a suitable tool to assess exposure to toxins overcoming the disadvantages of traditional methods. Urine constitutes an accessible biological matrix in biomonitoring studies. Mycotoxins are secondary metabolites produced naturally by filamentous fungi that produce a wide range of adverse health [...] Read more.

Human biomonitoring constitutes a suitable tool to assess exposure to toxins overcoming the disadvantages of traditional methods. Urine constitutes an accessible biological matrix in biomonitoring studies. Mycotoxins are secondary metabolites produced naturally by filamentous fungi that produce a wide range of adverse health effects. Thus, the determination of urinary mycotoxin levels is a useful tool for assessing the individual exposure to these food contaminants. In this study, a suitable methodology has been developed to evaluate the presence of aflatoxin B2 (AFB2), aflatoxin (AFG2), ochratoxin A (OTA), ochratoxin B (OTB), zearalenone (ZEA), and α-zearalenol (α-ZOL) in urine samples as exposure biomarkers. For this purpose, different extraction procedures, namely, the Solid Phase Extraction (SPE); Dispersive Liquid–Liquid Microextraction (DLLME); and Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) methods were assessed, followed by Liquid Chromatography coupled to Quadrupole Time of Flight Mass Spectrometry with Electrospray Ionization (LC-ESI-QTOF-MS) determination. Then, the proposed methodology was applied to determine mycotoxin concentrations in 56 human urine samples from volunteers and to estimate the potential risk of exposure. The results obtained revealed that 55% of human urine samples analyzed resulted positive for at least one mycotoxin. Among all studied mycotoxins, only AFB2, AFG2, and OTB were detected with incidences of 32, 41, and 9%, respectively, and levels in the range from <LOQ to 69.42 µg/L. Risk assessment revealed a potential health risk, obtaining MoE values < 10,000. However, it should be highlighted that few samples were contaminated, and that more data about mycotoxin excretion rates and their BMDL10 values are needed for a more accurate risk assessment. Full article

(This article belongs to the Section Mycotoxins)

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3 pages, 204 KiB

Open AccessEditorial

Editorial on the Special Issue “Botulinum Toxin for the Treatment of Neurological Disorders: Where We Are and Where We Need to Go”

by Mandar Jog and Alfonso Fasano

Toxins 2022, 14(1), 41; https://doi.org/10.3390/toxins14010041 - 5 Jan 2022

Viewed by 1642

Abstract

Over the past 30 years, botulinum toxin (BoNT) has seen an ever-expanding use in disorders afflicting the nervous system [...] Full article

(This article belongs to the Special Issue Botulinum Toxin for the Treatment of Neurological Disorders—Where We Are and Where We Need to Go)

15 pages, 455 KiB

Open AccessArticle

Foodborne Toxigenic Agents Investigated in Central Italy: An Overview of a Three-Year Experience (2018–2020)

by Valeria Russini, Carlo Corradini, Maria Laura De Marchis, Tatiana Bogdanova, Sarah Lovari, Paola De Santis, Giuseppina Migliore, Stefano Bilei and Teresa Bossù

Toxins 2022, 14(1), 40; https://doi.org/10.3390/toxins14010040 - 5 Jan 2022

Cited by 4 | Viewed by 2859

Abstract

Foodborne diseases (FBDs) represent a worldwide public health issue, given their spreadability and the difficulty of tracing the sources of contamination. This report summarises the incidence of foodborne pathogens and toxins found in food, environmental and clinical samples collected in relation to diagnosed [...] Read more.

Foodborne diseases (FBDs) represent a worldwide public health issue, given their spreadability and the difficulty of tracing the sources of contamination. This report summarises the incidence of foodborne pathogens and toxins found in food, environmental and clinical samples collected in relation to diagnosed or suspected FBD cases and submitted between 2018 and 2020 to the Food Microbiology Unit of the Istituto Zooprofilattico Sperimentale del Lazio e della Toscana (IZSLT). Data collected from 70 FBD investigations were analysed: 24.3% of them started with an FBD diagnosis, whereas a further 41.4% involved clinical diagnoses based on general symptomatology. In total, 5.6% of the 340 food samples analysed were positive for the presence of a bacterial pathogen, its toxins or both. Among the positive samples, more than half involved meat-derived products. Our data reveal the probable impact of the COVID-19 pandemic on the number of FBD investigations conducted. In spite of the serious impact of FBDs on human health and the economy, the investigation of many foodborne outbreaks fails to identify the source of infection. This indicates a need for the competent authorities to continue to develop and implement a more fully integrated health network. Full article

(This article belongs to the Special Issue Foodborne Toxins and Related Diseases and Outbreaks)

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10 pages, 289 KiB

Open AccessArticle

Effectiveness of Botulinum Toxin on Pain in Stroke Patients Suffering from Upper Limb Spastic Dystonia

by Carlo Trompetto, Lucio Marinelli, Laura Mori, Luca Puce, Chiara Avanti, Elena Saretti, Giulia Biasotti, Roberta Amella, Filippo Cotellessa, Domenico A. Restivo and Antonio Currà

Toxins 2022, 14(1), 39; https://doi.org/10.3390/toxins14010039 - 5 Jan 2022

Cited by 8 | Viewed by 2560

Abstract

This observational study aimed at investigating pain in stroke patients with upper limb spastic dystonia. Forty-one consecutive patients were enrolled. A 0–10 numeric rating scale was used to evaluate pain at rest and during muscle tone assessment. Patients were asked to indicate the [...] Read more.

This observational study aimed at investigating pain in stroke patients with upper limb spastic dystonia. Forty-one consecutive patients were enrolled. A 0–10 numeric rating scale was used to evaluate pain at rest and during muscle tone assessment. Patients were asked to indicate the most painful joint at passive mobilization (shoulder, elbow, wrist-fingers). The DN4 questionnaire was administered to disclose neuropathic pain. All patients were assessed just before and 1 month after incobotulinumtoxin-A treatment. Pain was present in 22 patients, worsened or triggered by passive muscle stretching. DN4 scored < 4 in 20 patients. The most painful joints were wrist–fingers in 12 patients, elbow in 5 patients and shoulder in the remaining 5 patients. Both elbow and wrist–fingers pain correlated with muscle tone. BoNT-A treatment reduced pain in all the joints, including the shoulder. We discussed that nociceptive pain is present in a vast proportion of patients with upper limb spastic dystonia. BoNT-A treatment reduced both spastic dystonia and pain in all the joints but the shoulder, where the effect on pain could be mediated by the reduction of pathological postures involving the other joints. Full article

(This article belongs to the Special Issue Treatment Applications of Botulinum Toxins in the Multidisciplinary and Integrated Management of Pain Syndromes)

12 pages, 1217 KiB

Open AccessArticle

Development of an Extraction Method of Aflatoxins and Ochratoxin A from Oral, Gastric and Intestinal Phases of Digested Bread by In Vitro Model

by Paula Llorens, Renata Pietrzak-Fiećko, Juan Carlos Moltó, Jordi Mañes and Cristina Juan

Toxins 2022, 14(1), 38; https://doi.org/10.3390/toxins14010038 - 4 Jan 2022

Cited by 9 | Viewed by 2222

Abstract

Validated extraction methods from in vitro digestion phases are necessary to obtain a suitable bioaccessibility study of mycotoxins in bakery products. The bakery industry produces bread with different ingredients to enrich the nutritional properties of this product and protect it from fungal growth. [...] Read more.

Validated extraction methods from in vitro digestion phases are necessary to obtain a suitable bioaccessibility study of mycotoxins in bakery products. The bakery industry produces bread with different ingredients to enrich the nutritional properties of this product and protect it from fungal growth. This bread can be contaminated by AFB₁, AFB₂, AFG₁, AFG₂ and OTA, so an extraction method was developed to analyse these five legislated mycotoxins in digested phases of two types of bread, one with wheat and the other with wheat and also enriched with Cucurbita Maxima Pepo at 20%. The studied “in vitro” digestion model consists of oral, gastric and duodenal phases, each one with different salt solutions and enzymes, that can affect the extraction and most probably the stability of the mycotoxins. The proposed method is a liquid–liquid extraction using ethyl acetate by extract concentration. These analytes and components have an important effect on the matrix effect (MEs) in the analytical equipment, therefore, validating the method and obtaining high sensitivity will be suitable. In the proposed method, the highest MEs were observed in the oral phase of digested pumpkin bread (29 to 15.9 %). Regarding the accuracy, the recoveries were above 83% in the digested duodenal wheat bread and above 76 % in the digested duodenal pumpkin wheat bread. The developed method is a rapid, easy and optimal option to apply to oral, gastric and duodenal phases of digested bread contaminated at a level of established maximum levels by European legislation (RC. 1881/2006) for food. Full article

(This article belongs to the Special Issue Mycotoxin Contamination and Food Safety)

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22 pages, 3365 KiB

Open AccessArticle

Shedding Lights on Crude Venom from Solitary Foraging Predatory Ant Ectatomma opaciventre: Initial Toxinological Investigation

by Lucas Ian Veloso Correia, Fernanda Van Petten de Vasconcelos Azevedo, Fernanda Gobbi Amorim, Sarah Natalie Cirilo Gimenes, Lorena Polloni, Mariana Alves Pereira Zoia, Mônica Soares Costa, Jéssica Peixoto Rodrigues, Kelly A. Geraldo Yoneyama, Jean Carlos Santos, Eliane Candiani Arantes, Veridiana de Melo Rodrigues, Luiz Ricardo Goulart and Renata Santos Rodrigues

Toxins 2022, 14(1), 37; https://doi.org/10.3390/toxins14010037 - 4 Jan 2022

Cited by 3 | Viewed by 4120

Abstract

Some species of primitive predatory ants, despite living in a colony, exercise their hunting collection strategy individually; their venom is painful, paralyzing, digestive, and lethal for their prey, yet the toxins responsible for these effects are poorly known. Ectatomma opaciventre is a previously [...] Read more.

Some species of primitive predatory ants, despite living in a colony, exercise their hunting collection strategy individually; their venom is painful, paralyzing, digestive, and lethal for their prey, yet the toxins responsible for these effects are poorly known. Ectatomma opaciventre is a previously unrecorded solitary hunting ant from the Brazilian Cerrado. To overcome this hindrance, the present study performed the in vitro enzymatic, biochemical, and biological activities of E. opaciventre to better understand the properties of this venom. Its venom showed several proteins with masses ranging from 1–116 kDa, highlighting the complexity of this venom. Compounds with high enzymatic activity were described, elucidating different enzyme classes present in the venom, with the presence of the first L-amino acid oxidase in Hymenoptera venoms being reported. Its crude venom contributes to a state of blood incoagulability, acting on primary hemostasis, inhibiting collagen-induced platelet aggregation, and operating on the fibrinolysis of loose red clots. Furthermore, the E. opaciventre venom preferentially induced cytotoxic effects on lung cancer cell lines and three different species of Leishmania. These data shed a comprehensive portrait of enzymatic components, biochemical and biological effects in vitro, opening perspectives for bio-pharmacological application of E. opaciventre venom molecules. Full article

(This article belongs to the Special Issue Toxinologic and Pharmacological Investigation of Venomous Arthropods)

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14 pages, 2101 KiB

Open AccessEditor’s ChoiceReview

A Systematic Review and Meta-Analysis of Efficacy of Botulinum Toxin A for Neuropathic Pain

by Anupam Datta Gupta, Suzanne Edwards, Jessica Smith, John Snow, Renuka Visvanathan, Graeme Tucker and David Wilson

Toxins 2022, 14(1), 36; https://doi.org/10.3390/toxins14010036 - 3 Jan 2022

Cited by 21 | Viewed by 5465

Abstract

We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum toxin A (BoNT-A) in neuropathic pain (NP) in addition to quality of life (QOL), mental health, and sleep [...] Read more.

We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum toxin A (BoNT-A) in neuropathic pain (NP) in addition to quality of life (QOL), mental health, and sleep outcomes. We conducted a Cochrane Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria analysis of RCTs from the following data sources: EMBASE, CINAHL, WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, Cochrane database, Cochrane Clinical Trial Register, Australia New Zealand Clinical Trials Registry, and EU Clinical Trials Register. Meta-analysis of 17 studies showed a mean final VAS reduction in pain in the intervention group of 2.59 units (95% confidence interval: 1.79, 3.38) greater than the mean for the placebo group. The overall mean difference for sleep, Hospital Anxiety and Depression Scale (HADS) anxiety, HADS depression, and QOL mental and physical sub-scales were, respectively, 1.10 (95% CI: −1.71, 3.90), 1.41 (95% CI: −0.61, 3.43), −0.16 (95% CI: −1.95, 1.63), 0.85 (95% CI: −1.85, 3.56), and −0.71 (95% CI: −3.39, 1.97), indicating no significance. BoNT-A is effective for NP; however, small-scale RCTs to date have been limited in evidence. The reasons for this are discussed, and methods for future RCTs are developed to establish BoNT-A as the first-line agent. Full article

(This article belongs to the Section Bacterial Toxins)

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